Skin illnesses such as atopic dermatitis, contact dermatitis, urticaria and prurigo are often accompanied by itch (itch: an unpleasant feeling of skin making one fell like scratching). The itch causes not only a vicious cycle of exacerbation of pathology and increasing of the itch due to induced scratch behavior but also a lowered efficiency in daily life and job as well as sleep problem that leads to deterioration of Quality of Life (hereinafter QOL). Hence, the suppression of the itch is important in the treatment of skin illness along with the suppression of inflammation response in the skin.
Drugs containing various synthetic steroids are widely used for the treatment of skin illnesses and significant therapeutic effects have been achieved. However, steroid drugs for external use have no direct suppressing effect toward the itch and are considered to suppress the itch in an indirect manner by suppressing the inflammation response. Since the itch in atopic dermatitis and the like are considered to be the phenomenon arising from histamine from mast cells, antihistamine drugs and anti-allergic drugs are often administered as drugs for internal or external use.
In recent years, drugs for external use containing tacrolimus, an immune-suppressing drug have been used (for example, see Hidemi Nakagawa et al., “Tacrolimus ointment for atopic dermatitis”, Lancet, Vol. 344 (1994), p. 883). Similarly to steroid drugs, the major mechanism of action of tacrolimus is suppression of inflammatory response and the suppression of the scratch behavior by tacrolimus is observed in the experiments using disease model mouse of atopic dermatitis (for example, see Naoki Inagaki and Hiroichi Nagai, “Evaluation of drugs for the treatment of atopic dermatitis in mice”, Folia Pharmacologica Japonica, Vol. 127 (2006), No. 2, p. 109-115).
Recently, internal use of cyclosporin, an immune-suppressing drug, has been under consideration for patients with severe atopic dermatitis which cannot be controlled by traditional general therapies or for patients difficult to treat with steroids (for example, see Camp, R. D. et al., “Cyclosporin A in severe, therapy-resistant atopic dermatitis”, report of an international workshop, April 1993, British Journal of Dermatology, Vol. 129, No. 2 (1993), p. 217-220). In Japan, the use of cyclosporin for patients with severe atopic dermatitis has been approved under certain conditions.
In other approaches, the methods and drugs that control itch or inflammatory response in gene level have been investigated. For example, WO 2006/006722 discloses a cell regeneration-, proliferation- and differentiation-controlling agent containing particular proteins comprising cholecystokinin, a neuropeptide or analogues thereof and a method for treating in which cell regeneration, proliferation and differentiation are involved such as obesity, diabetes, immune disorder, liver disorder, alimentary disorder, tissue damage in cosmetic surgery by administering such agent and a use of cholecystokinin as preventive and/or therapeutic agent for immune disorders such as atopic dermatitis.
Also, Japanese Unexamined Patent Application Publication (Translation of PCT Application) No. 2009-526754 discloses an invention relating to a pharmaceutical composition comprising at least one pharmaceutical agent as an active ingredient, nanostructures for facilitating intake in vivo and liquid and a therapeutic agent for itch using a neuropeptide.